Rai is a new regulator of neural progenitor migration and glioblastoma invasion

Barbara Ortensi, Daniela Osti, Serena Pellegatta, Federica Pisati, Paola Brescia, Lorenzo Fornasari, Daniel Levi, Paolo Gaetani, Piergiuseppe Colombo, Anna Ferri, Silvia Nicolis, Gaetano Finocchiaro, Giuliana Pelicci

Research output: Contribution to journalArticle

Abstract

The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knockdown impairs progenitor migration to the olfactory bulb. Its expression is retained in GBM stem/progenitor cells where it exerts the same promigratory activity. Rai silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple-signaling pathways, yet it always leads to reduced expression of proinvasive genes.

Original languageEnglish
Pages (from-to)817-832
Number of pages16
JournalStem Cells
Volume30
Issue number5
DOIs
Publication statusPublished - May 2012

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Keywords

  • Adult neural stem and progenitor cells
  • Cancer stem cells
  • Cell migration
  • Glioblastoma
  • Invasion
  • Shc

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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